Table 1.
Summary of DHX9 variant alleles
| Individual(s) | Phenotype | Position (hg19) | Nucleotide and protein | De novo | Allele count and frequency (gnomAD) | CADD score | REVEL score | Conservation (phylop100way) |
|---|---|---|---|---|---|---|---|---|
| 1 | NDD | chr1: 182822498G>A | c.422G>A (p.Arg141Gln) | yes | absent | 22.3 | 0.20 | 6.67 |
| 2 (BAB15412) | NDD | chr1: 182845191T>G | c.1822T>G (p.Cys608Gly) | yes | absent | 24.3 | 0.31 | 7.24 |
| 3 and 12 | NDD | chr1: 182856253G>C | c.3497G>C (p.Arg1166Pro) | yes | absent | 23.8 | 0.67 | 6.74 |
| 4 | NDD | chr1: 182825663A>AA | c.627−4dupA (p.?) | yes | absent | – | – | – |
| 5 | NDD | chr1: 182835663G>A | c.1417G>A (p.Val473Ile) | yes | 1 htz; 1 in 141,456 | 26.3 | 0.34 | 9.14 |
| 6 | NDD | chr1: 182856244A>G | c.3488A>G (p.Lys1163Arg) | yes | absent | 22.0 | 0.27 | 6.17 |
| 7 | NDD | chr1: 182850561G>T | c.2786+1G>T (p.?) | unknown | absent | 35.0 | – | 9.05 |
| 8 | NDD | chr1: 182827250C>T | c.685C>T (p.Arg229Ter) | yes | absent | 38 | – | 4.29 |
| 9 | NDD | chr1: 182829219G>A | c.1232G>A (p.Gly411Glu) | yes | absent | 25.1 | 0.73 | 9.09 |
| 10 | NDD | chr1: 182845626CGA>C | c.2075_2076delGA (p.Glu693GlyfsTer7) | yes | absent | – | – | – |
| 11 | NDD | chr1: 182847239G>A | c.2282G>A (p.Arg761Gln) | yes | absent | 32 | 0.90 | 7.33 |
| 13 | NDD | chr1: 182847238C>T | c.2281C>T (p.Arg761Trp) | yes | absent | 29 | 0.91 | 2.36 |
| 14 | NDD | chr1: 182856543C>T | c.3787C>T (p.Gln1263Ter) | unknown | absent | 37 | – | 0.83 |
| Iossifov et al.19,a | NDD | chr1: 182852665G>A | c.3155G>A (p.Arg1052Gln) | yes | absent | 27.2 | 0.21 | 9.10 |
| BAB4646a | NDD | chr1: 182827238G>A | c.674−1G>A (p.?) | unknown | absent | 35 | – | 8.95 |
| M42-1a | NDD | chr1: 182847247C>T | c.2290C>T (p.Arg764Ter) | unknown | absent | 36 | – | 1.75 |
| 15 (BAB12399) | CMT | chr1: 182849656A>G | c.2537A>G (p.Asp846Gly) | yes | absent | 26.7 | 0.21 | 6.84 |
| 16 (BAB14692) | CMT | chr1: 182848543G>C | c.2510G>C (p.Arg837Thr) | unknown | absent | 31 | 0.15 | 5.39 |
| 17 (BAB704) | CMT | chr1: 182856519G>A | c.3763G>A (p.Ala1255Thr) | unknown | absent | 16.19 | 0.14 | 2.18 |
Abbreviations: NDD, neurodevelopmental disorder; CMT, Charcot-Marie-Tooth disease; CADD, Combined Annotation Dependent Depletion; gnomAD, Genome Aggregation Database; htz, heterozygote; REVEL, Rare Exome Variant Ensemble Learner.
a
Limited clinical details are available, or there is evidence that multilocus pathogenic variation contributes to a blended phenotype. See the supplemental notes for additional details.